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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:30:43 UTC
HMDB IDHMDB01198
Secondary Accession Numbers
  • HMDB06015
Metabolite Identification
Common NameLeukotriene C4
DescriptionLeukotriene C4 (LTC4) is a cysteinyl leukotriene (CysLT), a family of potent inflammatory mediators. Eosinophils, one of the principal cell types recruited to and activated at sites of allergic inflammation, is capable of elaborating lipid mediators, including leukotrienes derived from the oxidative metabolism of arachidonic acid (AA). Potentially 'activated' eosinophils may elaborate greater quantities of LTC4, than normal eosinophils. These activated eosinophils thus are 'primed' for enhanced LTC4 generation in response to subsequent stimuli. Some recognized priming stimuli are chemoattractants (e.g., eotaxin, PAF) that may participate in the recruitment of eosinophils to sites of allergic inflammation. The mechanisms by which chemoattractants and other activating cytokines (e.g., interleukin (IL)-5) or extracellular matrix components (e.g., fibronectin) enhance eosinophil eicosanoid formation are pertinent to the functions of these eicosanoids as paracrine mediators of allergic inflammation. Some eosinophil-derived eicosanoids may be active in down-regulating inflammation. It is increasingly likely that eicosanoids synthesized within cells, including eosinophils, may have intracellular (e.g., intracrine) roles in regulating cell functions, in addition to the more recognized activities of eicosanoids as paracrine mediators of inflammation. Acting extracellularly, the cysteinyl leukotrienes (CysLTs) LTC4 and its extracellular derivatives, LTD4 and LTE4 are key paracrine mediators pertinent to asthma and allergic diseases. Based on their receptor-mediated capabilities, they can elicit bronchoconstriction, mucous hypersecretion, bronchial hyperresponsiveness, increased microvascular permeability, and additional eosinophil infiltration. Eosinophils are a major source of CysLTs and have been identified as the principal LTC4 synthase expressing cells in bronchial mucosal biopsies of asthmatic subjects. (PMID: 12895596 )Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.
Structure
Thumb
Synonyms
  1. (R-(R*,S*-(E,E,Z,Z)))-N-(S-(1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl)-N-L-gamma-glutamyl-L-cysteinyl)-Glycine
  2. 5S,6R-Ltc
  3. 5S-Hydroxy,6R-(S-glutathionyl),7E,9E,11Z,14Z-eicosatetraenoate
  4. 5S-Hydroxy,6R-(S-glutathionyl),7E,9E,11Z,14Z-eicosatetraenoic acid
  5. L-gamma-Glutamyl-S-[(1R,2E,4E,6Z,9Z)-1-[(1S)-4-carboxy-1-hydroxybutyl]-2,4,6,9-pentadecatetraenyl]-L-cysteinyl-glycine
  6. Leucotriene C4
  7. Leukotriene C
  8. Leukotriene C1
  9. Leukotriene C4
  10. LTC
  11. LTC4
  12. [R-[R*,S*-(E,E,Z,Z)]]-N-[S-[1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl]-N-L-gamma-glutamyl-L-cysteinyl]-Glycine 5S,6R-LTC4
Chemical FormulaC30H47N3O9S
Average Molecular Weight625.774
Monoisotopic Molecular Weight625.303300807
IUPAC Name(5S,6R,7E,9E,11Z,14Z)-6-{[(2R)-2-[(4S)-4-amino-4-carboxybutanamido]-2-[(carboxymethyl)carbamoyl]ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
Traditional IUPAC Name(5S,6R,7E,9E,11Z,14Z)-6-{[(2R)-2-[(4S)-4-amino-4-carboxybutanamido]-2-(carboxymethylcarbamoyl)ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
CAS Registry Number72025-60-6
SMILES
CCCCC\C=C/C\C=C/C=C/C=C/[C@@H](SC[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)NCC(O)=O)[C@@H](O)CCCC(O)=O
InChI Identifier
InChI=1S/C30H47N3O9S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-25(24(34)15-14-17-27(36)37)43-21-23(29(40)32-20-28(38)39)33-26(35)19-18-22(31)30(41)42/h6-7,9-13,16,22-25,34H,2-5,8,14-15,17-21,31H2,1H3,(H,32,40)(H,33,35)(H,36,37)(H,38,39)(H,41,42)/b7-6-,10-9-,12-11+,16-13+/t22-,23-,24-,25+/m0/s1
InChI KeyGWNVDXQDILPJIG-NXOLIXFESA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassPeptides
Sub ClassN/A
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Hydroxy Fatty Acids
  • Leukotrienes
  • Organic Compounds
  • Thia Fatty Acids
  • Unsaturated Fatty Acids
Substituents
  • Acyclic Alkene
  • Alpha Amino Acid Or Derivative
  • Carboxamide Group
  • Carboxylic Acid
  • Hydroxyeicosatetraenoic Acid
  • N Acyl Alpha Amino Acid
  • N Acylglycine
  • N Substituted Alpha Amino Acid
  • Primary Aliphatic Amine (Alkylamine)
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
  • Thioether
  • Tricarboxylic Acid Derivative
Direct ParentPeptides
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Prostaglandin and leukotriene metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
  • Endoplasmic reticulum
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0025 g/LALOGPS
logP0.04ALOGPS
logP-0.015ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)1.8ChemAxon
pKa (Strongest Basic)9.31ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area216.35ChemAxon
Rotatable Bond Count25ChemAxon
Refractivity168.51ChemAxon
Polarizability68.38ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Intestine
  • Lens
  • Leukocyte
  • Neutrophil
  • Platelet
  • Skin
  • Smooth Muscle
Pathways
NameSMPDB LinkKEGG Link
Arachidonic Acid MetabolismSMP00075map00590
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.7E-5 +/- 2.3E-5 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.001359 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified0.00006 +/- 0.00003 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified6.989e-05 +/- 2.767e-05 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000133 +/- 3.454e-05 uMChildren (1-13 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000101 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified7.996e-05 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.791e-05 +/- 4.798e-06 uMNot SpecifiedNot SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00024 +/- 0.000065 uMAdult (>18 years old)BothEczema details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000153 +/- 1.711e-05 uMAdult (>18 years old)Not SpecifiedSpinal cord injuries (acute stage) details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000557 uMNot SpecifiedNot SpecifiedAIDS details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000185 +/- 7.628e-05 uMChildren (1-13 years old)Not SpecifiedAseptic meningitis details
Cerebrospinal Fluid (CSF)Detected and Quantified<7.996e-05 uMNot SpecifiedNot Specifiedclosed head injury details
Cerebrospinal Fluid (CSF)Detected and Quantified1.343e-05 uMAdult (>18 years old)Maleglutathione synthetase deficiency, acute metabolic crisis details
Cerebrospinal Fluid (CSF)Detected and Quantified<7.996e-05 uMNot SpecifiedNot Specifiedgunshot wound details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000422 uMNot SpecifiedNot SpecifiedHIV-Seropositive details
Cerebrospinal Fluid (CSF)Detected and Quantified2.399e-05 uMNot SpecifiedNot SpecifiedHIV-Seropositive, Dementia details
Cerebrospinal Fluid (CSF)Detected and Quantified<0.000160 uMNot SpecifiedNot Specifiedhydrocephalus details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00413 +/- 0.000611 uMNot SpecifiedNot Specifiedsubarachnoid hemorrhage with cerebral vasospasm details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000280 uMNot SpecifiedNot SpecifiedHIV-Seropositive (Neurologically normal) details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00130 +/- 0.000227 uMNot SpecifiedNot Specifiedsubarachnoid hemorrhage without cerebral vasospasm details
Associated Disorders and Diseases
Disease References
Eczema
  1. Hua Z, Fei H, Mingming X: Evaluation and interference of serum and skin lesion levels of leukotrienes in patients with eczema. Prostaglandins Leukot Essent Fatty Acids. 2006 Jul;75(1):51-5. Epub 2006 Jun 6. Pubmed: 16757158
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022484
KNApSAcK IDNot Available
Chemspider ID4444133
KEGG Compound IDC02166
BioCyc IDLEUKOTRIENE-C4
BiGG ID2212273
Wikipedia LinkLeukotriene C4
NuGOwiki LinkHMDB01198
Metagene LinkHMDB01198
METLIN ID3681
PubChem Compound5280493
PDB IDNot Available
ChEBI ID16978
References
Synthesis ReferenceRokach, Joshua; Young, Robert N.; Kakushima, Masatoshi; Lau, Cheuk-Kun; Seguin, Rick; Frenette, Richard; Guindon, Yvan. Synthesis of leukotrienes. New synthesis of natural leukotriene A4. Tetrahedron Letters (1981), 22(11), 979-82.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sjolinder M, Tornhamre S, Claesson HE, Hydman J, Lindgren J: Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1. J Lipid Res. 1999 Mar;40(3):439-46. Pubmed: 10064732
  2. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. Pubmed: 15537867
  3. Lane SJ, Lee TH: Mast cell effector mechanisms. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2. Pubmed: 8939179
  4. Sawazaki Y: [Leukotriene B4, leukotriene C4 and prostaglandin E2 in the serum, synovial fluid and synovium in patients with rheumatoid arthritis] Nippon Ika Daigaku Zasshi. 1989 Dec;56(6):559-64. Pubmed: 2558123
  5. Heimburger M, Palmblad JE: Effects of leukotriene C4 and D4, histamine and bradykinin on cytosolic calcium concentrations and adhesiveness of endothelial cells and neutrophils. Clin Exp Immunol. 1996 Mar;103(3):454-60. Pubmed: 8608646
  6. Romero R, Wu YK, Mazor M, Hobbins JC, Mitchell MD: Increased amniotic fluid leukotriene C4 concentration in term human parturition. Am J Obstet Gynecol. 1988 Sep;159(3):655-7. Pubmed: 3421265
  7. Paoletti P, Gaetani P, Grignani G, Pacchiarini L, Silvani V, Rodriguez y Baena R: CSF leukotriene C4 following subarachnoid hemorrhage. J Neurosurg. 1988 Oct;69(4):488-93. Pubmed: 3418380
  8. De Servi S, Ricevuti G, Mazzone A, Pasotti D, Bramucci E, Angoli L, Specchia G: Transcardiac release of leukotriene C4 by neutrophils in patients with coronary artery disease. J Am Coll Cardiol. 1991 Apr;17(5):1125-8. Pubmed: 2007712
  9. Koshino T, Takano S, Houjo T, Sano Y, Kudo K, Kihara H, Kitani S, Takaishi T, Hirai K, Ito K, Morita Y: Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the peripheral blood leukocytes of asthmatics. Biochem Biophys Res Commun. 1998 Jun 18;247(2):510-3. Pubmed: 9642160
  10. Richter L, Hesselbarth N, Eitner K, Schubert K, Bosseckert H, Krell H: Increased biliary secretion of cysteinyl-leukotrienes in human bile duct obstruction. J Hepatol. 1996 Nov;25(5):725-32. Pubmed: 8938552
  11. Sternfeld M, Fink A, Bentwich Z, Eliraz A: The role of acupuncture in asthma: changes in airways dynamics and LTC4 induced LAI. Am J Chin Med. 1989;17(3-4):129-34. Pubmed: 2633615
  12. Ponicke K, Forster W: Influence of leukotriene C4 on aggregation and on malondialdehyde formation of human blood platelets. Biomed Biochim Acta. 1984;43(8-9):S459-62. Pubmed: 6440558
  13. Angi MR, Bettero A, Filippi F, Salvalaio L, Benassi CA: [Quantitative evaluation of conjunctival irritation by simultaneous determination of histamine, serotonin and leukotriene C4 in tears] Ophtalmologie. 1987 Oct-Dec;1(4):509-11. Pubmed: 3153930
  14. Cruz JR, Cano F, Razin E, Acheson DW, Keusch GT: Fecal excretion of leukotriene C4 during human disease due to Shigella dysenteriae. J Pediatr Gastroenterol Nutr. 1995 Feb;20(2):179-83. Pubmed: 7714683
  15. Zijlstra FJ, Wilson JH: 15-HETE is the main eicosanoid present in mucus of ulcerative proctocolitis. Prostaglandins Leukot Essent Fatty Acids. 1991 May;43(1):55-9. Pubmed: 1652771
  16. Matsumoto S, Hayashi Y, Kinoshita I, Ikata T, Yamamoto S: Immunoaffinity purification of prostaglandin E2 and leukotriene C4 prior to radioimmunoassay: application to human synovial fluid. Ann Clin Biochem. 1993 Jan;30 ( Pt 1):60-8. Pubmed: 8434868
  17. Talbot SF, Atkins PC, Goetzl EJ, Zweiman B: Accumulation of leukotriene C4 and histamine in human allergic skin reactions. J Clin Invest. 1985 Aug;76(2):650-6. Pubmed: 2411760
  18. Kloprogge E, de Leeuw AJ, de Monchy JG, Kauffman HF: Cellular communication in leukotriene C4 production between eosinophils and neutrophils. Int Arch Allergy Appl Immunol. 1989;90(1):20-3. Pubmed: 2509375
  19. Damtew B, Spagnuolo PJ: Leukotriene C4 from vascular endothelium enhances neutrophil adhesiveness. Prostaglandins Leukot Essent Fatty Acids. 1997 Feb;56(2):111-6. Pubmed: 9051719
  20. Schauer U, Eckhart A, Muller R, Gemsa D, Rieger CH: Enhanced leukotriene C4 production by peripheral eosinophilic granulocytes from children with asthma. Int Arch Allergy Appl Immunol. 1989;90(3):201-6. Pubmed: 2512259
  21. Bandeira-Melo C, Weller PF: Eosinophils and cysteinyl leukotrienes. Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):135-43. Pubmed: 12895596

Enzymes

General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Catalyzes the transfer of the glutamyl moiety of glutathione to amino acids and dipeptide acceptors. Alternatively, glutathione can be hydrolyzed to give Cys-Gly and gamma glutamate. Isoform 3 seems to be inactive.
Gene Name:
GGT1
Uniprot ID:
P19440
Molecular weight:
61409.67
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves glutathione conjugates (By similarity).
Gene Name:
GGT7
Uniprot ID:
Q9UJ14
Molecular weight:
70466.015
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in enzyme activator activity
Specific function:
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
Gene Name:
LTC4S
Uniprot ID:
Q16873
Molecular weight:
16566.465
Reactions
Leukotriene A4 + Glutathione → Leukotriene C4details
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves glutathione conjugates (By similarity).
Gene Name:
GGT6
Uniprot ID:
Q6P531
Molecular weight:
50508.83
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Not Available
Gene Name:
GGT7
Uniprot ID:
A0PJJ9
Molecular weight:
62565.3
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves the gamma-glutamyl peptide bond of glutathione conjugates, but maybe not glutathione itself. Converts leukotriene C4 (LTC4) to leukotriene D4 (LTD4).
Gene Name:
GGT5
Uniprot ID:
P36269
Molecular weight:
62331.75
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails

Transporters

General function:
Involved in ATP binding
Specific function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular weight:
171589.5